Abstract

This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD), which can be sporadic or part of Carney complex and primary bilateral macro nodular adrenal hyperplasia (PBMAH). The bilateral nature of the tumors suggests the existence of an underlying genetic predisposition. PPNAD and Carney complex are mainly due to germline-inactivating mutations of PRKAR1A, coding for a regulatory subunit of PKA, whereas PBMAH genetic seems more complex. However, genome-wide approaches allowed the identification of a new tumor suppressor gene, ARMC5, whose germline alteration could be responsible for at least 25% of PBMAH cases. Unilateral adrenocortical tumors are more frequent, mostly adenomas. The Wnt/beta-catenin pathway can be activated in both benign and malignant tumors by CTNNB1 mutations and by ZNRF3 inactivation in adrenal cancer (ACC). Some other signaling pathways are more specific of the tumor dignity. Thus, somatic mutations of cAMP/PKA pathway genes, mainly PRKACA, coding for the catalytic alpha-subunit of PKA, are found in cortisol-secreting adenomas, whereas IGF-II overexpression and alterations of p53 signaling pathway are observed in ACC. Genome-wide approaches including transcriptome, SNP, methylome and miRome analysis have identified new genetic and epigenetic alterations and the further clustering of ACC in subgroups associated with different prognosis, allowing the development of new prognosis markers.

Highlights

  • Adrenocortical tumors can be unilateral or bilateral, secreting or non-secreting various types of adrenal steroids depending on tumor type

  • In a study including 9 primary pigmented nodular adrenal disease (PPNAD) (5 with macro nodules), 3 sporadic cortisolsecreting adrenocortical adenomas (ACA) with protein kinase A regulatory subunit 1-alpha (PRKAR1A) somatic mutation and 1 heterogeneous tumor with an adrenocortical carcinomas (ACC) developing within an ACA, beta-catenin accumulation was found in all tumor types

  • As in benign adrenocortical tumors, germline mutations responsible for familial syndromes predisposing to ACC, allowed the identification of signaling pathways involved in cancer development, somatic alterations of these pathways being further screened in sporadic cases of ACC (Libè et al 2007, Espiard & Bertherat 2015)

Read more

Summary

Introduction

Adrenocortical tumors can be unilateral or bilateral, secreting or non-secreting various types of adrenal steroids depending on tumor type. Concerning PDE8B, the screening of 216 adrenocortical tumors negative for mutations in PRKAR1A, PDE11A and GNAS, identified 6 different variants of PDE8B in a total 7 patients (1 ACC, 1 PPNAD, 2 PBMAH, 2 secreting ACA and 1 non-secreting ACA).

Objectives
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call